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        ISSN: 2652-4414

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                              Medical & Surgical Case Reports
        Research Article                                               Niknamian S and Zaminpira S. Ann Med &Surg Case Rep: AMSCR-100050

        The Historical/Evolutionary Cause and Possible Treatment of Pandemic
                        Covid-19 (Sars-Cov-2, 2019-Coronavirus)
        Niknamian S1* and Zaminpira S2
        1
          Department of Military Medicine,American Military University and Liberty University, USA
        2
          Department of Phycology and Psychiatry,American Beirut University, Beirut, Lebanon

        Corresponding author: Sorush Niknamian, Department of Military Medicine, American Military University and Liberty University,
        *

        USA, Tel: 989121939806; Email: So.niknamian@gmail.com
        Citation: Niknamian S and Zaminpira S (2020) The Historical/Evolutionary Cause and Possible Treatment of Pandemic Covid-19
        (Sars-Cov-2, 2019-Coronavirus). Ann Med &Surg Case Rep: AMSCR-100050
        Received date: 11 April, 2020; Accepted date: 20 April, 2020; Published date: 27 April, 2020

            Abstract
            Background: A virus is a small infectious agent that replicates only inside the living cells of an organism. Viruses can infect all
            types of life forms, from animals and plants to microorganisms, including bacteria and archaea. In evolution, viruses are an important
            means of horizontal gene transfer, which increases genetic diversity in a way analogous to sexual reproduction.Influenza (Including
            (COVID-19), is an infectious disease caused by an influenza virus. Some viruses especially smallpox, throughout history, has killed
            between 300-500 million people in its 12,000-year existence.As modern humans increased in numbers, new infectious diseases
            emerged, including SARS-CoV-2. We have two groups of virus, RNA and DNA viruses. The most brutal viruses are RNA ones like
            COVID-19 (Sars-CoV-2).
            Introduction:Coronaviruses are a group of viruses that cause diseases in mammals and birds. In humans, coronaviruses cause respi-
            ratory tract infections that are typically mild, such as some cases of the common cold (among other possible causes, predominantly
            rhinoviruses), though rarer forms can be lethal, such as SARS, MERS, and COVID-19. Symptoms vary in other species: in chickens,
            they cause an upper respiratory tract disease, while in cows and pigs they cause diarrhea. Coronaviruses constitute the subfamily
            Orthocoronavirinae, The genome size, coronaviruses ranges from approximately 27 to 34 kilobases, the largest among known RNA
            viruses.
            Discussions and Results:We have researched from the first virus in the planet to the last mutated version which is SARS-COV-2. We
            have collected many informative data in tables and figures to reach the main cause of 2019-Coronavirus and calculated the probability
            and estimated deaths in the current time. We have discussed about the possible treatment and prevention of the virus and did algebraic
            calculations on the epidemiology, the size and even the future of this pandemic. The only era which any virus had not been epidemic,
            were through world war 2, were the German scientists had found the way to fight any viral infections which is very important and can
            help scientists to reach the main treatment of the new 2019-Coronavirus. We have sorted the deadly and non-deadly coronaviruses
            and explained how this epidemic had begun through Evolutionary Medicine (EM). The result of the article is that 16% of the whole
            population in the world has been contaminated which is 1248000000 of 7.8 billion people world-wide. SARS-CoV-2 is an RNA
            Virus. its nucleic acid is single-stranded RNA (ssRNA). The polarity of this virus is positive-sense ((+) ssRNA). Positive-sense viral
            RNA is similar to mRNA and thus can be immediately translated by the host cell. Recombination in RNA viruses appears to be an
            adaptation for coping with genome damage. Recombination can occur infrequently between animal viruses of the same species but
            of divergent lineages. The resulting recombinant viruses may sometimes cause an outbreak of infection in humans. RNA viruses have
            very high mutation rates This is one reason why it is difficult to make effective vaccines to prevent diseases caused by RNA viruses.
            The resulting recombinant viruses causes an outbreak of infection in humans.
            Conclusion:In conclusion, the mutation of the SARS-CoV and influenza viruses through Drift and Reassortment is the main cause

        Citation: Niknamian S and Zaminpira S (2020) The Historical/Evolutionary Cause and Possible Treatment of Pandemic Covid-19 (Sars-Cov-2, 2019-Corona-
        virus). Ann Med &Surg Case Rep: AMSCR-100050

Ann Med & Surg Case Rep, an open access journal
ISSN: 2652-4414
Annals of Medical & Surgical Case Reports - GRF Publishers
2                                                                                                                              Volume 02; Issue 03

          of SARS-CoV-2 through natural selection, Lamarckian Evolution and coevolution which caused this RNA virus so powerful, unpre-
          dicted and different in the genome size and nations worldwide. The first Pandemic of Influenza was first detected in 1732 and this
          virus evolved through natural selection till 2019 which caused the worldwide pandemic of SARS-CoV-2. Based on many studies,
          inhalation of Ozone plus Sulfur Dioxide, increasing the amounts of L-Glutathione (Which is low in children and older adults and this
          is the main reason why older adults and children die from this disease.) plus Viral Phage Therapy (VPT) which we discussed fully
          in this article can be the possible prime treatment of SARS-CoV-2 infection. The seasonal temperature cannot be useful in control-
          ling/reducing the pandemic of this virus since the natural selection, Lamarckian Evolution and high mutation of the virus helps its
          survival. No antiviral drugs will be useful against SARS-CoV-2 because of high rate of mutation and primarily adaptation of the virus
          to the drugs and even the environmental Temperature.

        Keywords:         COVID-19 (SARS-CoV-2);Drift; Fibonacci                   even rarer, although there are notable exceptions such as influenza.
        Series; Influenza; Lamarckian Evolution; L-Glutathione; Natural            Most viruses are species-specific and would have posed no threat
        Selection;Ozone; Positive-Sense ((+) ssRNA Sulfur Dioxide;                 to humans[14].
        Reassortment; Pandemic); Viral Phage Therapy                                      The rare epidemics of viral diseases originating in animals
                                                                                   would have been short-lived because the viruses were not fully
        Introduction                                                               adapted to humans [15] and the human populations were too
                                                                                   small to maintain the chains of infection[16]. Other, more ancient,
        Brief History of Viruses
                                                                                   viruses have been less of a threat. Herpes viruses first infected
        Prehistory: The world, new infectious diseases emerged, including          the ancestors of modern humans over 80 million years ago[17].
        those caused by viruses[1]. Earlier, humans lived in small, isolated       Humans have developed a tolerance to these viruses, and most
        communities, and most epidemic diseases did not exist[2,3].                are infected with at least one species[18]. Records of these milder
        Smallpox, which is the most lethal and devastating viral infection         virus infections are rare, but it is likely that early hominids suffered
        in history, first emerged among agricultural communities in India          from colds, influenza and diarrhoea caused by viruses just as
        about 11,000 years ago[4]. The virus, which only infected humans,          humans do today. More recently evolved viruses cause epidemics
        probably descended from the poxviruses of rodents [5]. Humans              and pandemics[17]. The influenza virus is one that seems to have
        probably came into contact with these rodents, and some people             crossed the species barrier from ducks and water fowl to pigs and
        became infected by the viruses they carried. When viruses cross            from there to humans. It is possible that a fatal plague in the Middle
        this so-called “species barrier”, their effects can be severe, [6]         East at the time of the late 18th Dynasty was associated with this
        and humans may have had little natural resistance. Contemporary            transmission at Amarna [19-20].
        humans lived in small communities, and those who succumbed to              Influenza:Influenza, commonly known as the flu, is an infectious
        infection either died or developed immunity.                               disease caused by an influenza virus [21-25]. Symptoms can be
               This acquired immunity is only passed down to offspring             mild to severe [25]. The most common symptoms include: high
        temporarily, by antibodies in breast milk and other antibodies             fever, runny nose, sore throat, muscle and joint pain, headache,
        that cross the placenta from the mother’s blood to the unborn              coughing, and feeling tired just like Sars-CoV-2[21]. These
        child’s. Therefore, sporadic outbreaks probably occurred in                symptoms typically begin two days after exposure to the virus and
        each generation. In about 9000 BC, when many people began to               most last less than a week [21]. The cough, however, may last
        settle on the fertile flood plains of the River Nile, the population       for more than two weeks [21]. In children, there may be diarrhea
        became dense enough for the virus to maintain a constant presence          and vomiting, but these are not common in adults [26]. Diarrhea
        because of the high concentration of susceptible people [7]. Other         and vomiting occur more commonly in gastroenteritis, which is an
        epidemics of viral diseases that depend on large concentrations of         unrelated disease and sometimes inaccurately referred to as stomach
        people, such as mumps, rubella and polio, also first occurred at           flu or the 24-hour flu[26]. Complications of influenza may include
        this time [8]. The Neolithic age, which began in the Middle East in        viral pneumonia, secondary bacterial pneumonia, sinus infections,
        about 9500 BC, was a time when humans became farmers [9].                  and worsening of previous health problems such as asthma or heart
                                                                                   failure [22,25]. Three of the four types of influenza viruses affect
               This agricultural revolution embraced the development of            humans: Type A, Type B, and Type C[22,27]. Type D has not been
        monoculture and presented an opportunity for the rapid spread of           known to infect humans, but is believed to have the potential to
        several species of plant viruses [10]. The divergence and spread           do so [27,28]. Usually, the virus is spread through the air from
        of sobemoviruses-southern bean mosaic virus-date from this                 coughs or sneezes [21](Table 1-7). This is believed to occur
        time[11]. The spread of the potyviruses of potatoes, and other             mostly over relatively short distances [29]. It can also be spread by
        fruits and vegetables, began about 6,600 years ago. [10] About             touching surfaces contaminated by the virus and then touching the
        10,000 years ago the humans who inhabited the lands around the             eyes, nose, or mouth [25,29,30-35]. A person may be infectious to
        Mediterranean basin began to domesticate wild animals. Pigs,               others both before and during the time they are showing symptoms
        cattle, goats, sheep, horses, camels, cats and dogs were all kept          [25,36-40]. The infection may be confirmed by testing the throat,
        and bred in captivity[12]. These animals would have brought their          sputum, or nose for the virus [45-50]. A number of rapid tests are
        viruses with them[13]. The transmission of viruses from animals            available; however, people may still have the infection even if the
        to humans can occur, but such zoonotic infections are rare and             results are negative [22]. A type of polymerase chain reaction that
        subsequent human-to-human transmission of animal viruses is                detects the virus’s RNA is more accurate [22](Figure 1-3).

        Citation: Niknamian S and Zaminpira S (2020) The Historical/Evolutionary Cause and Possible Treatment of Pandemic Covid-19 (Sars-Cov-2, 2019-Corona-
        virus). Ann Med &Surg Case Rep: AMSCR-100050

Ann Med & Surg Case Rep, an open access journal
ISSN: 2652-4414
Annals of Medical & Surgical Case Reports - GRF Publishers
3                                                                                                                              Volume 02; Issue 03

                                                                                   Figure 2: Symptoms of influenza, with fever and cough the most
                                                                                   common symptoms [20-22].
        Figure 1:Influenza virus, magnified approximately 100,000 times,
        Specialty: Infectious disease, Symptoms: Fever, runny nose, sore
        throat, muscle and joint pain, headache, coughing, feeling tired,
        Usual onset: One to four days after exposure, Duration: 1 week,
        Causes: Influenza viruses.Prevention: Hand washing, influenza
        vaccine, surgical masks, Frequency: 3-5 million severe cases per
        year. Deaths: Up to 650,000 respiratory deaths per year[1-3].

                     Symptom                    Sensitivity         Specificity
                       Fever                      68-86%              25-73%
                      Cough                       84-98%              7-29%
                  Nasal congestion                68-91%              19-41%

             Note: All three findings, especially fever, were less sensitive in
                               people over 60 years of age.
                                                                                   Figure 3: 29 yr. old with H1N1 with high inflammation in the
         Table 1:Most sensitive symptoms for diagnosing influenza [1-3].           lungs and respiratory systems.

        Citation: Niknamian S and Zaminpira S (2020) The Historical/Evolutionary Cause and Possible Treatment of Pandemic Covid-19 (Sars-Cov-2, 2019-Corona-
        virus). Ann Med &Surg Case Rep: AMSCR-100050

Ann Med & Surg Case Rep, an open access journal
ISSN: 2652-4414
Annals of Medical & Surgical Case Reports - GRF Publishers
4                                                                                                                              Volume 02; Issue 03

                  Figure 4: Seasonal risk areas for influenza: November-April (blue), April-November (red), and year-round (yellow) [21].

        List of epidemics of Plagues
             Death toll (estimate)          Location                     Date                        Event                         Disease
                                                                                                                      Unknown, possibly typhus, typhoid
                  75,000-100,000             Greece                  429-426 BC                Plague of Athens
                                                                                                                       fever or viral hemorrhagic fever
                   5-10 million          Roman Empire        165-180 (possibly up to 190)      Antonine Plague           Unknown, possibly smallpox
                                             Europe                    250-266                 Plague of Cyprian         Unknown, possibly smallpox
            25-50 million; 40% of      Europe, Egypt and
                                                                       541-542                Plague of Justinian                   Plague
                 population                West Asia
                                             Rome                        590                 Roman Plague of 590                    Plague
                    > 100,000           Ctesiphon, Persia              627-628                 Plague of Sheroe                     Plague
                                          British Isles                664-689                   Plague of 664                      Plague

                                                                                               735-737 Japanese
                                              Japan                    735-737                                                     Smallpox
                                                                                              smallpox epidemic

                                       Byzantine Empire,
                                                                       746-747                Plague of 746-747                     Plague
                                       West Asia, Africa

          20-200 million; 20-60% of     Europe, Asia and                                                                            Plague
                                                                      1331-1353                  Black Death
             European population          North Africa                                                                             Y. pestis
                                        England and later                                      Sweating sickness       Unknown, possibly an unknown
                     > 10,000                                         1485-1551
                                       continental Europe                                     (multiple outbreaks)         species of hantavirus

                                                                Table 2: 15th century and earlier.

        Citation: Niknamian S and Zaminpira S (2020) The Historical/Evolutionary Cause and Possible Treatment of Pandemic Covid-19 (Sars-Cov-2, 2019-Corona-
        virus). Ann Med &Surg Case Rep: AMSCR-100050

Ann Med & Surg Case Rep, an open access journal
ISSN: 2652-4414
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            Death toll (estimate)       Location             Date                     Event                              Disease                   Ref.
            5-15 million (80% of                                           Cocoliztli Epidemic of 1545-
                                         Mexico           1545-1548                                            Possibly Salmonella enterica      [50-53]
                population)                                                            1548
           2-2.5 million (50% of
                                         Mexico           1576-1580         Cocoliztli epidemic of 1576        Possibly Salmonella enterica      [50-53]
                population)
                   280,000                 Italy          1629-1631         Italian plague of 1629-1631                   Plague                 [54-60]
                   100,000               England          1665-1666           Great Plague of London                      Plague                 [61-67]
                   76,000                Austria             1679             Great Plague of Vienna                      Plague                     -
                   40,000                 France             1668                                                         Plague                   [68]
                                                                                                             Unknown cause. Latest research
                                                                                                                suggests epidemic(s) of lep-
                                        Southern
                                                                                                              tospirosis with Weil syndrome.
                                      New England,
                                                                                                               Classic explanations include
           30-90% of population       especially the      1616-1619        1616 New England epidemic                                             [58-59]
                                                                                                               yellow fever, bubonic plague,
                                       Wampanoag
                                                                                                             influenza, smallpox, chickenpox,
                                         people
                                                                                                            typhus, and syndemic infection of
                                                                                                                hepatitis B and hepatitis D.

                  24,148[32]           Netherlands        1663-1664                      -                                Plague                     -
            > 20,100 in London           London           1563-1564            1563 London plague                         Plague                     -
                                         London           1592-1593           1592-93 London plague                       Plague                     -
                                      Seneca nation       1592-1596                      -                               Measles                   [54]
                                          Spain           1596-1602                      -                                Plague                   [55]
                                      South America       1600-1650                      -                               Malaria                   [56]
                                         England             1603                        -                                Plague                   [57]
                                          Egypt              1609                        -                                Plague                     -
                                     Wyandot people          1634                        -                              Smallpox                   [61]
                                      Thirteen Colo-                        Massachusetts smallpox epi-
                                                             1633                                                       Smallpox                     -
                                           nies                                      demic
                                         England             1636                                                         Plague                   [62]
          > 19,900 in London and
               outer parishes             China           1641-1644                                                       Plague                   [63]
                                          Spain           1647-1652           Great Plague of Seville                     Plague
                                         Central
                                                             1648                                                      Yellow fever                [64]
                                         America
                                           Italy             1656                 Naples Plague                           Plague                   [65]
                                      Thirteen Colo-
                                                             1657                        -                               Measles                   [61]
                                           nies
                                          Spain           1676-1685                      -                                Plague                   [67]

                                      Thirteen Colo-
                                                             1687                        -                               Measles                   [68]
                                           nies
                                      Thirteen Colo-
                                                             1690                        -                             Yellow fever                  -
                                           nies
                                                                    Table 3: 16-17th centuries.

        Citation: Niknamian S and Zaminpira S (2020) The Historical/Evolutionary Cause and Possible Treatment of Pandemic Covid-19 (Sars-Cov-2, 2019-Corona-
        virus). Ann Med &Surg Case Rep: AMSCR-100050

Ann Med & Surg Case Rep, an open access journal
ISSN: 2652-4414
Annals of Medical & Surgical Case Reports - GRF Publishers
6                                                                                                                                Volume 02; Issue 03

                     -                  Canada, New France               1702-1703                  -                  Smallpox                [69]

            > 18,000 (36% of                                                                 Great Smallpox
                                              Iceland                    1707-1709                                     Smallpox                 -
               population)                                                                     Epidemic
                                                                                           Great Northern War
                                         Denmark,Sweden                  1710-1712                                       Plague                 -
                                                                                            plague outbreak

                                         Thirteen Colonies               1713-1715                  -                   Measles                [70]

                                        Canada, New France               1714-1715                  -                   Measles                [71]

                                                                                             Great Plague of
                                                  France                 1720-1722                                       Plague                [72]
                                                                                               Marseille

                                         Thirteen Colonies               1721-1722                  -                  Smallpox                [73]

                                         Thirteen Colonies                  1729                    -                   Measles                [74]

                                                  Spain                     1730                    -                 Yellow fever

                                         Thirteen Colonies               1732-1733                  -                  Influenza               [75]

                                        Canada, New France                  1733                    -                  Smallpox                [76]

                  > 50,000                    Balkans                       1738          Great Plague of 1738           Plague

                                         Thirteen Colonies                  1738                    -                  Smallpox                [77]

                                         Thirteen Colonies               1739-1740                  -                   Measles

                                                  Italy                     1743                    -                    Plague                [78]

                                         Thirteen Colonies                  1747                    -                   Measles

                                           North America                 1755-1756                  -                  Smallpox

                                           North America                    1759                    -                   Measles                [79]

                                     North America, West Indies             1761                    -                  Influenza

                                     North America, present-day
                                                                            1763                    -                  Smallpox                [80]
                                           Pittsburgh area.
                                                                                            Russian plague of
                  > 50,000                        Russia                 1770-1772                                       Plague
                                                                                               1770-1772

                                      Pacific Northwest natives             1770s                   -                  Smallpox                [81]

                                           North America                    1772                    -                   Measles

              > 2,000,000                         Persia                    1772            1772 Persia plague           Plague                [8]

        Citation: Niknamian S and Zaminpira S (2020) The Historical/Evolutionary Cause and Possible Treatment of Pandemic Covid-19 (Sars-Cov-2, 2019-Corona-
        virus). Ann Med &Surg Case Rep: AMSCR-100050

Ann Med & Surg Case Rep, an open access journal
ISSN: 2652-4414
Annals of Medical & Surgical Case Reports - GRF Publishers
7                                                                                                                                 Volume 02; Issue 03

                                              England                    1775-1776                                      Influenza              [82]

                                                  Spain                     1778                    -                 Dengue fever             [83]

                                                                                            North American
                                           Plains Indians                1780-1782                                      Smallpox               [84]
                                                                                           smallpox epidemic

                                           Pueblo Indians                   1788                    -                   Smallpox               [85]

                                           United States                    1788                    -                   Measles

                                    New South Wales, Australia           1789-1790                  -                   Smallpox               [86]

                                                                                                                      Influenza and
                                           United States                    1793                    -
                                                                                                                     Epidemic Typhus
                                                                                              Yellow Fever
                                           United States                 1793-1798          Epidemic of 1793,         Yellow fever             [87]
                                                                                               resurgences
                                                                       Table 4: 18thcentury.

           Death toll (estimate)                  Location                  Date                    Event                       Disease            Ref.
                  1,000,000                         Russia               1852-1860         Third cholera pandemic               Cholera               [88]
                  1,000,000                       Worldwide              1889-1890         1889-1890 flu pandemic              Influenza              [83]
                  > 100,000                   Asia, Europe               1816-1826          First cholera pandemic              Cholera               [89]
                  > 100,000           Asia, Europe, North America        1829-1851        Second cholera pandemic               Cholera               [89]
                   40,000                            Fiji                   1875         1875 Fiji Measles outbreak            Measles                [81]
                  > 20,000                         Canada                1847-1848        Typhus epidemic of 1847          Epidemic typhus            [69]
                   > 9,000                   India, Germany              1881-1896         Fifth cholera pandemic               Cholera               [89]
                                                                                        Cholera epidemic of Copenha-
                    4,737                Copenhagen, Denmark                1853                                                Cholera               [73]
                                                                                                  gen 1853
                    3,164                         Montreal                  1885                        -                      Smallpox         Timeline
                   > 3,000           Central Coast, British Columbia     1862-1863                      -                      Smallpox               [78]

        Citation: Niknamian S and Zaminpira S (2020) The Historical/Evolutionary Cause and Possible Treatment of Pandemic Covid-19 (Sars-Cov-2, 2019-Corona-
        virus). Ann Med &Surg Case Rep: AMSCR-100050

Ann Med & Surg Case Rep, an open access journal
ISSN: 2652-4414
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                                               England                     1854         Broad Street cholera outbreak          Cholera             [74]
                                                 Spain                   1800-1803                                           Yellow fever          [86]
                                        Ottoman Empire, Egypt              1801                      -                      Bubonic plague         [87]
                                             United States                 1803                      -                       Yellow fever            -
                                                 Egypt                     1812                      -                          Plague               -
                                           Ottoman Empire                  1812                      -                          Plague             [88]
                                                 Malta                     1813                      -                          Plague               -
                                               Romania                     1813               Caragea’s plague                  Plague               -
                                                Ireland                  1816-1819                   -                         Typhus                -
                                             United States               1820-1823                   -                       Yellow fever            -
                                                 Spain                     1821                                              Yellow fever          [90]
                                       New South Wales, Australia          1828                      -                        Smallpox             [91]
                                             Netherlands                   1829              Groningen epidemic                Malaria               -
                                            South Australia                1829                      -                        Smallpox             [92]
                                                  Iran                   1829-1835                   -                      Bubonic plague         [93]
                                                 Egypt                     1831                      -                         Cholera           [94,95]
                                            Plains Indians               1831-1834                   -                        Smallpox               -
                                           England, France                 1832                      -                         Cholera               -
                                            North America                  1832                      -                         Cholera             [96]
                                             United States                 1833                      -                         Cholera               -
                                             United States                 1834                      -                         Cholera               -
                                                 Egypt                   1834-1836                                          Bubonic plague       [96,97]
                                             United States                 1837                       -                        Typhus                -
                                             Great Plains                1837-1838       1837-38 smallpox epidemic            Smallpox             [98]
                                              Dalmatia                     1840                       -                         Plague               -
                    616                      South Africa                  1840                       -                       Smallpox               -
                                             United States                 1841                       -                      Yellow fever            -
                                             United States                 1847                       -                      Yellow fever            -
                                              Worldwide                  1847-1848                    -                       Influenza            [99]
                                                 Egypt                     1848                       -                        Cholera           [96,97]
                                            North America                1848-1849                    -                        Cholera               -
                                             United States                 1850                       -                      Yellow fever            -
                                            North America                1850-1851                    -                       Influenza              -
                                             United States                 1851                       -                        Cholera            [100]
                                             United States                 1852                       -                      Yellow fever
                                           Ottoman Empire                  1853                       -                         Plague            [101]
                                             United States                 1855                       -                      Yellow fever
                                              Worldwide                  1855-1960         Third plague pandemic            Bubonic plague        [102]
                                                 Portugal                  1857                       -                      Yellow fever
                                            Victoria, Australia            1857                       -                       Smallpox            [103]
                                      Europe, North America, South
                                                America                  1857-1859                     -                       Influenza        [104-111]
                                              Middle East                1863-1879         Fourth cholera pandemic             Cholera            [112]
                                                 Egypt                     1865                       -                        Cholera           [96,97]
                                           Russia, Germany               1866-1867                    -                        Cholera              -
                                               Australia                   1867                       -                        Measles              -
                                                  Iraq                     1867                                                 Plague            [105]
                                               Argentina                 1852-1871                     -                     Yellow fever         [106]
                                               Germany                   1870-1871                     -                      Smallpox              -
                                            Russian Empire                 1877                        -                        Plague            [108]
                                                 Egypt                     1881                        -                       Cholera           [96,97]
                                              West Africa                  1900                        -                     Yellow fever
                                                                      Table 5:19thcentury.

        Citation: Niknamian S and Zaminpira S (2020) The Historical/Evolutionary Cause and Possible Treatment of Pandemic Covid-19 (Sars-Cov-2, 2019-Corona-
        virus). Ann Med &Surg Case Rep: AMSCR-100050

Ann Med & Surg Case Rep, an open access journal
ISSN: 2652-4414
Annals of Medical & Surgical Case Reports - GRF Publishers
9                                                                                                                               Volume 02; Issue 03

             Death toll
                                       Location                  Date                       Event                         Disease               Ref.
             (estimate)
                                     Congo Basin              1896-1906                                               Trypanosomiasis           [109]
             > 800,000            Europe, Asia, Africa        1899-1923            Sixth cholera pandemic                 Cholera               [85]
                  113                San Francisco            1900-1904                        -                      Bubonic plague            [110]
                                        Uganda                1900-1920                        -                      Trypanosomiasis           [111]
                                         Egypt                   1902                          -                          Cholera              [96,97]
                  22                     India                   1903                          -                      Bubonic Plague            [112]
                   4                   Fremantle                 1903                          -                      Bubonic plague            [113]
               40,000                    China                1910-1912               1910 China plague               Bubonic plague            [114]
                                                                               1915 Encephalitis lethargica pan-    Encephalitis lethar-
             1.5 million              worldwide               1915-1926                                                                         [115]
                                                                                           demic                            gica
               up to                                                                                                 Influenza Spanish
                                      worldwide               1918-1920                  Spanish flu                                            [116]
            100,000,000                                                                                                   Flu Virus
                                        Russia                1918-1922                        -                           Typhus                 -
                                                                                 1924 Los Angeles pneumonic
                  30                  Los Angeles                1924                                                Pneumonic plague             -
                                                                                       plague outbreak
                  43                 Croydon, UK                 1937         Croydon epidemic of typhoid fever        Typhoid fever            [117]
                   -                     Egypt                1942-1944                        -                          Malaria              [96,97]
                   -                     China                   1946                          -                      Bubonic plague
                   -                     Egypt                   1946                          -                      Relapsing fever          [96,97]
                   -                     Egypt                   1947                          -                          Cholera              [96,97]
             2,000,000                worldwide               1957-1958                    Asian flu                     Influenza              [118]
                                      worldwide               1961-1975           Seventh cholera pandemic                Cholera               [110]
                   4                    Sweden                   1963                                                    Smallpox            [119,120]
             1,000,000                worldwide               1968-1969                 Hong Kong flu                    Influenza              [118]
                   5                  Netherlands                1971                                                  Poliomyelitis            [121]
                                                                                 1972 outbreak of smallpox in
                  35                  Yugoslavia                 1972                                                    Smallpox                 -
                                                                                         Yugoslavia
                                     United States            1972-1973                   London flu                     Influenza              [122]
               15,000                    India                   1974          1974 smallpox epidemic of India           Smallpox               [123]
                               worldwide(commenced in
            > 32,000,000                                     1960-present           HIV/AIDS pandemic                   HIV/AIDS                [124]
                                    Congo Basin)
                                    South America               1990s                          -                          Cholera                 -
                  52                     India                   1994           1994 plague epidemic in Surat              Plague               [125]
                  231                 worldwide               1996-2001                        -                           vCJD                   -
                   -                  West Africa                1996                          -                         Meningitis               -
                                                                                1998-99 Malaysia Nipah virus         Nipah virus infec-
                  105                  Malaysia               1998-1999                                                                         [126]
                                                                                         outbreak                          tion
                                    Central America              2000                          -                       Dengue fever             [127]

                                                                        Table 6:20thcentury.

        Citation: Niknamian S and Zaminpira S (2020) The Historical/Evolutionary Cause and Possible Treatment of Pandemic Covid-19 (Sars-Cov-2, 2019-Corona-
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           Death toll (estimate)           Location              Date                       Event                        Disease               Ref.
                   > 400                    Nigeria              2001                          -                         Cholera              [128]
                                         South Africa            2001                          -                         Cholera              [129]
                                                                                                                     SARS corona-
                    349                      China            2002-2004                SARS outbreak                                          [130]
                                                                                                                        virus
                                                                                                                     SARS corona-
                    299                   Hong Kong           2002-2004                SARS outbreak                                          [131]
                                                                                                                        virus
                                                                                                                     SARS corona-
                    37                      Taiwan            2002-2004                SARS outbreak                                          [132]
                                                                                                                        virus
                                                                                                                     SARS corona-
                    44                      Canada            2002-2004                SARS outbreak                                          [133]
                                                                                                                        virus
                                                                                                                     SARS corona-
                    33                    Singapore           2002-2004                SARS outbreak                                          [134]
                                                                                                                        virus
                     -                      Algeria              2003                          -                         Plague               [135]
                     -                   Afghanistan             2004                          -                     Leishmaniasis            [136]
                     -                    Bangladesh             2004                          -                         Cholera              [137]
                     -                     Indonesia             2004                          -                      Dengue fever            [138]
                     -                      Senegal              2004                          -                         Cholera              [139]
                     7                      Sudan                2004                          -                          Ebola               [140]
                                             Mali                2005                                                 Yellow fever            [141]
                    27                    Singapore              2005         2005 dengue outbreak in Singapore       Dengue fever            [142]
                                        Luanda, Angola           2006                          -                         Cholera            [143-166]
                                     Ituri Province, Demo-
                    61               cratic Republic of the      2006                          -                         Plague             [167,168]
                                             Congo
                    17                       India               2006                          -                         Malaria              [169]
                   > 50                      India               2006           2006 dengue outbreak in India         Dengue fever            [169]
                                                                                                                      Chikungunya
                                             India               2006              Chikungunya outbreaks                                      [170]
                                                                                                                         virus
                   > 50                    Pakistan              2006         2006 dengue outbreak in Pakistan        Dengue fever            [171]
                                          Philippines            2006                          -                      Dengue fever            [172]
                                     Democratic Republic
                    187                                          2007               Mwekaebola epidemic                   Ebola               [173]
                                        of the Congo
                                           Ethiopia              2007                          -                         Cholera              [174]
                    49                       India               2008                          -                         Cholera              [175]
                    10                       Iraq                2007             2007 Iraq cholera outbreak             Cholera              [176]
                                            Nigeria              2007                          -                      Poliomyelitis           [177]
                                     Puerto Rico; Domini-
                                                                 2007                          -                      Dengue fever            [178]
                                     can Republic; Mexico
                                           Somalia               2007                          -                         Cholera              [179]
                    37                      Uganda               2007                          -                          Ebola               [180]
                     -                     Vietnam               2007                          -                         Cholera              [181]
                     -                      Brazil               2008                          -                      Dengue fever            [182]
                     -                    Cambodia               2008                          -                      Dengue fever            [183]
                     -                       Chad                2008                          -                         Cholera              [184]

        Citation: Niknamian S and Zaminpira S (2020) The Historical/Evolutionary Cause and Possible Treatment of Pandemic Covid-19 (Sars-Cov-2, 2019-Corona-
        virus). Ann Med &Surg Case Rep: AMSCR-100050

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                                                                                                                     Hand, foot and
                      -                     China             2008-2017                       -                                               [185]
                                                                                                                     mouth disease
                      -                  Madagascar              2008                         -                      Bubonic plague           [186]
                      -                   Philippines            2008                         -                       Dengue fever            [187]
                      -                    Vietnam               2008                         -                         Cholera               [188]
                                                                               2008-2009 Zimbabwean cholera
                    4,293                 Zimbabwe            2008-2009                                                 Cholera               [189]
                                                                                         outbreak
                                                                               2009 Bolivian dengue fever epi-
                     18                    Bolivia               2009                                                 Dengue fever            [190]
                                                                                           demic
                     49                      India               2009          2009 Gujarat hepatitis outbreak         Hepatitis B            [191]
                      -             Queensland, Australia        2009                         -                       Dengue fever            [192]
                                          Worldwide              2009           Mumps outbreaks in the 2000s             Mumps
                                                                             2009-2010 West African meningitis
                    931                  West Africa          2009-2010                                                Meningitis             [193]
                                                                                        outbreak
                  203,000                 Worldwide              2009                 2009 flu pandemic                 Influenza           [194,195]
                                                                 2010-
            9,985 (May 2017)              Hispaniola                                Haiti cholera outbreak              Cholera             [196,197]
                                                                present
            > 4,500 (February        Democratic Republic      2011-pres-
                                                                                              -                         Measles            [198][199]
                  2014)                 of the Congo             ent
                                                              2011-pres-                                             Hand, foot and
                    170                    Vietnam                                            -                                             [200,201]
                                                                 ent                                                 mouth disease
                   > 350                   Pakistan              2011         2011 dengue outbreak in Pakistan        Dengue fever            [202]
            171 (as of 10 Janu-                                               2012 yellow fever outbreak in Dar-
                                        Darfur Sudan             2012                                                 Yellow fever            [203]
            ary 2013[update])                                                            fur, Sudan
                                                                                                                      Middle East
            862 (as of 13 Janu-                                  2012-        2012 Middle East respiratory syn-
                                          Worldwide                                                                   respiratory           [204-206]
            ary 2020[update])                                   present         drome coronavirus outbreak
                                                                                                                       syndrome
                    142                    Vietnam            2013-2014                       -                         Measles               [207]
                                     Worldwide, primarily                                                             Ebola virus
                  >> 11,300          concentrated in West     2013-2016      Ebola virus epidemic in West Africa     disease, Ebola         [208-210]
                                           Africa                                                                     virus virion
                    183                   Americas            2013-2015         2013-14 chikungunya outbreak          Chikungunya             [211]
                     40                  Madagascar           2014-2017       2014 Madagascar plague outbreak        Bubonic plague           [212]
                                                                                                                    Primarily Hepa-
                     36                      India            2014-2015         2014 Odisha jaundice outbreak       titis E, but also         [213]
                                                                                                                       Hepatitis A
                                                                                                                    Influenza A virus
                    2,035                    India               2015           2015 Indian swine flu outbreak                           [214][215][216]
                                                                                                                     subtype H1N1
                    ~53                   Worldwide           2015-2016          2015-16 Zika virus epidemic           Zika virus             [217]
               100’s (as of                                                     2016 yellow fever outbreak in
                                            Africa               2016                                                 Yellow fever            [218]
           1 April 2016[update])                                                          Angola
           3,886 (as of 30 No-                                   2016-
                                            Yemen                              2016-17 Yemen cholera outbreak           Cholera               [219]
          vember 2019[update])                                  present
             64 (as of 16 Au-                                                2017 Gorakhpur Japanese encephali-       Japanese en-
                                             India               2017                                                                         [220]
            gust 2017[update])                                                          tis outbreak                    cephalitis
             18 (as of Febru-                                                                                          Nipah virus
                                             India               2018        2018 Nipah virus outbreak in Kerala                              [221]
            ary 2020[update])                                                                                           infection

        Citation: Niknamian S and Zaminpira S (2020) The Historical/Evolutionary Cause and Possible Treatment of Pandemic Covid-19 (Sars-Cov-2, 2019-Corona-
        virus). Ann Med &Surg Case Rep: AMSCR-100050

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                                      Democratic Repub-         August
           2,253 (as of 20 Febru-                                                                                      Ebola virus
                                      lic of the Congo &         2018-          2018-19 Kivu Ebola epidemic                                     -
             ary 2020[update])                                                                                          disease
                                            Uganda              present
            >6,000 (by January       Democratic Republic         2019-       2019 measles outbreak in the Demo-
                                                                                                                        Measles                 -
                  2019)                 of the Congo            present         cratic Republic of the Congo
                                                                 2019-
                    83                      Samoa                               2019 Samoa measles outbreak             Measles                 -
                                                                present
               3,360 (as of                                      2019-
                                          Worldwide                             2019-20 coronavirus outbreak           COVID-19                 -
          6 March 2020[update])                                 present

                                                                     Table 7: 21st century.

               Coronaviruses are a group of viruses that cause diseases in         Discussion
        mammals and birds. In humans, coronaviruses cause respiratory
                                                                                          By mentioning all the facts, evolution and all the similarities
        tract infections that are typically mild, such as some cases of
                                                                                   from the viruses, we observe that all kinds of Flu including COVID-
        the common cold (among other possible causes, predominantly
                                                                                   19 which have been caused many deaths through epidemic and
        rhinoviruses), though rarer forms can be lethal, such as SARS,
                                                                                   pandemic of these giant but very small objects, all the viruses from
        MERS, and COVID-19. Symptoms vary in other species: in
                                                                                   the first one before the rise of the human in evolution, had been
        chickens, they cause an upper respiratory tract disease, while in
                                                                                   existed. Through my deep research, the first virus was or blue-
        cows and pigs they cause diarrhea. Coronaviruses constitute the
                                                                                   green algae, pre-date viruses and are one of the oldest forms of life
        subfamily Orthocoronavirinae, in the family Coronaviridae, order
                                                                                   on Earth(Figure 4).
        Nidovirales, and realm Ribavirin [31,32]. They are enveloped
        viruses with a positive-sense single-stranded RNA genome
        and a nucleocapsid of helical symmetry. The genome size of
        coronaviruses ranges from approximately 27 to 34 kilobases, the
        largest among known RNA viruses[33].

        Evolution
              The most recent common ancestor (MRCA) of all
        coronaviruses has been placed at around 8000 BCE [34]. The
        MRCAs of the Alpha-coronavirus line has been placed at about
        2400 BCE, the Beta-coronavirus line at 3300 BCE, the Gamma-
        coronavirus line at 2800 BCE, and the Delta-coronavirus line at
        about 3000 BCE. It appears that bats and birds, as warm-blooded
        flying vertebrates, are ideal hosts for the coronavirus gene source
        (with bats for Alpha-coronavirus and Beta coronavirus, and birds
        for Gamma-coronavirus and Delta-coronavirus) to fuel coronavirus
        evolution and dissemination [35]. Bovine coronavirus and canine
        respiratory coronaviruses diverged from a common ancestor in
        1951 [36]. Bovine coronavirus and human coronavirus OC43
        diverged around the 1890s. Bovine coronavirus diverged from the
        equine coronavirus species at the end of the 18th century [37]. The
        MRCA of human coronavirus OC43 has been dated to the 1950s
        [38]. MERS-CoV, although related to several bat coronavirus                Figure 4:Blue-green algae, pre-date viruses and are one of the
        species, appears to have diverged from these several centuries ago         oldest forms of life on Earth.
        [39]. The human coronavirus NL63 and a bat coronavirus shared
        an MRCA 563-822 years ago [40]. The most closely related bat               Results
        coronavirus and SARS-CoV diverged in 1986 [41]. A path of                        The researchers developed algorithms to compare the
        evolution of the SARS virus and keen relationship with bats have           protein shapes of 3,460 viruses and 1,620 cells. They found that
        been proposed. The coronaviruses have been coevolved with bats             442 protein folds were shared between cells and viruses, but 66
        for a long time and the ancestors of SARS-CoV first infected               folds were unique to viruses. To make sense of the data, the team
        the species of the genus Hipposideridae, subsequently spread to            arranged the protein folds into a tree that grew a new ‘branch’
        species of the Rhinolophidae and then to civets, and finally to            every time a new type of protein fold evolved. Wherever possible,
        humans[42-43]. Alpaca coronavirus and human coronavirus 229E               the team used fossil evidence to put an approximate date on the
        diverged before 1960 [44].                                                 budding of specific branches. For example, one particular protein

        Citation: Niknamian S and Zaminpira S (2020) The Historical/Evolutionary Cause and Possible Treatment of Pandemic Covid-19 (Sars-Cov-2, 2019-Corona-
        virus). Ann Med &Surg Case Rep: AMSCR-100050

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        fold was first seen in cyanobacteria (blue-green algae), and later appeared in all its descendants. By comparing when cyanobacteria first
        appeared in the fossil record (2.1 billion years ago) to when its offspring later emerged, they could establish this particular fold appeared
        around 2 billion years ago. According to Caetano-Anolles’s microbial family tree, viruses are ancient, however; they were not the first
        form of life. In fact, his family tree suggests viruses and bacteria share a common ancestor - a fully functioning, self-replicating cell that
        lived around 3.4 billion years ago, shortly after life first emerged on the planet. From this cell, bacteria have evolved in the direction of
        increasing complexity, while viruses have gradually shed genes they found they didn’t need, until they could no longer even reproduce
        on their own. A key step in the virus evolutionary journey seems to have come about around 1.5 billion years ago and that’s the age at
        which the 66 virus-specific protein folds came on the scene. These changes are to proteins in the virus’ outer coat-the machinery viruses
        use to break into host cells. For Charleston, the remarkable point about the study is how many proteins today’s bacteria and viruses have
        in common.Viral evolution, Primordial cellular origins and late adaptation to parasitism, Mob Genet Elements(Figure 5).

        Figure 5: The origin of the viruses was before the beginning the cellular ancestor of any species. Based on (Figure 5)and the mentioned
        era of the virus evolution, they have been there since 3.5 billion years ago when cyanobacteria begin to be existed. The main problem is
        to find what or which kinds of matter can fight this machine-like organism.

        Citation: Niknamian S and Zaminpira S (2020) The Historical/Evolutionary Cause and Possible Treatment of Pandemic Covid-19 (Sars-Cov-2, 2019-Corona-
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        Drift                                                                      Reassortment
               New viruses can also emerge by drift. Drift can refer to                   Reassortment, also known as antigenic shift, allows new
        genetic drift or antigenic drift. [45] Mutation and selection for the      viruses to evolve under both natural conditions and in artificial
        most advantageous variation of the virus takes place during this           cultures[45].Reassortment occurs in a similar way as chromosome
        form of evolution. Natural Selection and Lamarckian Evolution              crossover events, as two different viral strains may come in contact
        both caused the evolution of several viruses like Coronaviruses            and transfer some of their genetic information. This crossing-
        fast enough[45]. Antigenic mutants can evolve quickly due to               over event creates a mixture of the two viral strains, which may
        the high mutation rate in viruses. The cause of the antigenic drift        replicate as one hybrid virus that expresses traits from both original
        lies in the mechanisms of RNA synthesis itself. Mutations arise            viruses[46]. The mechanism of the evolutionary force of antigenic
        very easily simply due to the error prone RNA polymerase and its           shift allows influenza viruses to exchange genes with strains that
        lack of proofreading mechanisms. These mutations lead to subtle            infect different species. Under this mechanism, a human influenza
        changes in the HA and NA genes which completely changes the                virus could exchange genes with an avian strain, and that is
        infectious capabilities of the virus. These changes allow for almost       how pandemic strains arise. There have been three occurrences
        endless possibilities for new viral strains to arise [46,47] and it        of pandemics caused by antigenic shift since 1900, and it has
        is the antigenic drift of the HA and NA genes that allow for the           happened again today as we know as SARS-CoV-2[47].In fact,
        virus to infect humans that receive vaccines for other strains of the      the 1957 evolution of the H2N2 virus is thought to be a result
        virus[48]. This evolution occurs under the pressure of antibodies or       of Reassortment[45]. In this case, human H1N1 strains and avian
        immune system responses. Seven strains of human coronaviruses              influenza A genes were mixed [45]. Infecting tissue cultures can
        are known and four of them produce the generally mild symptoms             demonstrate how pathogenic qualities can evolve for a particular
        of the common cold: 1) Human coronavirus OC43 (HCoV-OC43),                 species even though the reasserted virus may be nonpathogenic for
        2) Human coronavirus HKU1, 3) Human coronavirus NL63                       another species [45]. A prime example of evolution under natural
        (HCoV-NL63, New Haven coronavirus), 4) Human coronavirus                   conditions is the Reassortment of two avian influenza strains that
        229E (HCoV-229E) and three coronaviruses that are potentially              were discovered in dead seals back in 1979 [45].
        fatal: 5) Middle East respiratory syndrome-related coronavirus
                                                                                         Based on research by an Inhalation of ozone and sulfur
        (MERS-CoV), previously known as novel coronavirus 2012 and
                                                                                   dioxide inhibited influenza virus growth in the nose of mice. Ozone
        HCoV-EMC, 6) Severe acute respiratory syndrome coronavirus
                                                                                   inhalation caused the more pronounced inhibition of influenza
        (SARS-CoV or “SARS-classic”), 7) Severe acute respiratory
                                                                                   virus growth: 0.6 ppm ozone for 3 hours’ post-virus exposure
        syndrome coronavirus 2 (SARS-CoV-2), previously known as
                                                                                   almost completely inhibited influenza virus growth in the nose,
        2019-nCoV or “novel coronavirus 2019”[45].
                                                                                   whereas sulfur dioxide (6 ppm for 7 days) causes only partial
                                                                                   inhibition of influenza growth in the nose. Neither gas altered
                                                                                   the propagation of influenza virus in the lungs of mice. Vesicular
                                                                                   stomatitis virus (VSV) growth was either unaffected by exposure
                                                                                   to ozone (0.9 ppm for 3 hours) or, when ozone exposure preceded
                                                                                   VSV exposure, the virus may have grown to slightly higher titer.
                                                                                   The inhibitory effect of ozone and sulfur dioxide on influenza
                                                                                   virus growth in nasal epithelium suggests a competitive interaction
                                                                                   between the chemical inhalant, the virus, and host tissues, with net
                                                                                   consequences for the pathogenesis of this disease. If the effects
                                                                                   of these inhalants are to be properly interpreted, they should be
                                                                                   determined for all major regions of virus growth and inhalant
                                                                                   deposition. Therefore; inhalation of Ozone plus Sulfur Dioxide
                                                                                   may inhibit the influenza virus growth in humans as well.
                                                                                          Another research indicates that Influenza virus was rendered
                                                                                   noninfectious for mice by in vitro exposure to relatively high
                                                                                   concentrations of sulfur and nitrogen mustards. Concentrations of
                                                                                   the mustards that abolished infectivity did not reduce the ability of
                                                                                   the virus to agglutinate erythrocytes. The parenteral administration
                                                                                   of nitrogen mustard had no effect on the course of infection with
                                                                                   influenza virus in mice.
                                                                                          There are several researches on the compound L-Glutathione
                                                                                   which contains high sulfur amounts and it is normally produced by
                                                                                   liver but the amounts vary in ages and sexes in its compound and
                                                                                   inhibits viral infection. These researches has done in in Vivo and
                                                                                   in Vitro with controlled groups double blind and received totally
        Figure 6: An antigenic shift, or Reassortment, which has the main          positive results and the treatment of the patients with several most
        result of novel and highly pathogenic strains of SARS-CoV-2 and            dangerous viral diseases including Coronaviruses.
        other DNA and RNA viruses like All types of fatal Influenza.

        Citation: Niknamian S and Zaminpira S (2020) The Historical/Evolutionary Cause and Possible Treatment of Pandemic Covid-19 (Sars-Cov-2, 2019-Corona-
        virus). Ann Med &Surg Case Rep: AMSCR-100050

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        Sulfur and Viruses
              Scientists have known about viruses that attack bacteria since the early twentieth century. In 1917, Felix d’Herelle, a French-
        Canadian microbiologist, and his colleagues successfully isolated phages that kill bacteria like E. coli, salmonella, and dysentery, and
        doctors used his so-called phage therapies to treat disease. But phage research lost steam in the 1950s in the face of penicillin and other
        powerful new antibiotics.Bacteria are living micro-organism which can be affected by viruses. The adaptation of bacteria to fight viruses
        are higher than human living cells. Therefore; this is the most important research on Phages against viruses which should be considered
        by scientists to fight against all viruses including 2019-Coronavirus. Paula Dalcin Martins and his colleagues reached positive results
        using Sulfur against many viruses. Basically If two viruses share a good number of genes, they are probably related like MERS, SARS
        and 2019-Coronavirus.The fewer genes they share, the more divergent their evolutionary paths. The most impressive article about sulfur
        against viruses has been published by Matthew B Sullivan which indicated Sulfur can kill and terminate any known viruses in eukaryotic
        host cells. Based on Sullivanstatements and articles, Sulfur and Phage Therapies can be one of the main treatment of viral diseases
        through coevolution hypothesis (coevolution occurs when two or more species reciprocally affect each other’s evolution through the
        process of natural selection like viruses and mammals.) including SARS-CoV-2(Figure 7-10).

                                                      Figure 7:Diagram of coronavirus Virion structure.

                                                       Figure 8: Illustration of a SARS-CoV-2 Virion.

        Citation: Niknamian S and Zaminpira S (2020) The Historical/Evolutionary Cause and Possible Treatment of Pandemic Covid-19 (Sars-Cov-2, 2019-Corona-
        virus). Ann Med &Surg Case Rep: AMSCR-100050

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                                Figure 9:MERS virus, Middle-East Respiratory Syndrome coronavirusVirion, (Camel Flu).

        Figure 10: A typical virus replication cycleincluding Sars-Cov-2019.2019-nCoV is sufficiently divergent from SARS-CoV to be
        considered a new human-infecting betacoronavirus. Although our phylogenetic analysis suggests that bats might be the original host of
        this virus, an animal sold at the seafood market in Wuhan might represent an intermediate host facilitating the emergence of the virus in
        humans. Importantly, structural analysis suggests that 2019-nCoV might be able to bind to the angiotensin-converting enzyme 2 receptor
        in humans. The future evolution, adaptation, and spread of this virus warrant urgent investigation.
              In Taxonomy, the family Coronaviridae is organized in 2 sub-families, 5 genera, 23 sub-genera and about 40 species: Coronaviridae
        - Orthocoronavirinae -Letovirinae-Alphaletovirus-Milecovirus and then Microhylaletovirus[3].
              MERS-CoV and Severe acute respiratory syndrome (SARS) are betacoronavirus derived from bats [2].Between November 2002
        and July 2003, an outbreak of SARS in southern China caused an eventual 8,098 cases, resulting in 774 deaths reported in 17 countries
        (9.6% fatality rate), with the majority of cases in mainland China and Hong Kong. No cases of SARS have been reported worldwide since
        2004. In late 2017[1-3]. Chinese scientists traced the virus through the intermediary of civets to cave-dwelling horseshoe bats in Yunnan
        province[220]. Therefore; through the lines above, SARS and COVID-19 outbreak was first observed in China.The coronaviruses
        HCoV-229E, -NL63, -OC43, and -HKU1 continually circulate in the human population and cause respiratory infections in adults and
        children world-wide [221].

        Citation: Niknamian S and Zaminpira S (2020) The Historical/Evolutionary Cause and Possible Treatment of Pandemic Covid-19 (Sars-Cov-2, 2019-Corona-
        virus). Ann Med &Surg Case Rep: AMSCR-100050

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               In the new Coronavirus, Genetic recombination which is              when get inside their hosts also mutates. Therefore; Each of these
        the process by a strand of DNA that is broken and then joined              coronaviruses get inside their host will have different symptoms
        to the end of a different DNA molecule. This can occur when                from mild into severe based on the host’s immune system response
        viruses infect cells simultaneously and studies of viral evolution         and other factors. Hence; all these SARS-CoV-2, will mutate and
        have shown that recombination has been rampant in the species              possible severe symptoms will occur based on the Reassortment of
        studied. [230]. Recombination is common to both RNA and DNA                the virus which have been described in page 22.The probability of
        viruses [108,220]. SARS-CoV-2 has undergone genetic change by              each person in the world who may contaminate with this virus is
        several mechanisms. These include a antigenic drift process where          7.8 Billion/479001600 equals 16.2838704505.
        individual bases in the RNA mutate to other bases. the mutations
                                                                                          This is the probability from the first time outbreak of the virus
        of this virus is silent means it does not change the protein that
                                                                                   means approximately 16% of the population infected by the virus.
        the gene encodes. And confers evolutionary advantages such as
                                                                                   So the near future of death or infected people from SARS-CoV-2
        resistance to antiviral drugs [210-220]. Therefore; we cannot
                                                                                   will be 1248000000. Based on high rates of mutation of 2019-
        mention there would be any possible antiviral drugs to resist this
                                                                                   Corovirus, each carrier of this deadly virus may/will contaminate
        kind of virus even in the future.
                                                                                   another living human. Therefore; all people will carry this virus
              SARS-CoV-2 is an RNA Virus. its nucleic acid is single-              in the near future. We do not know the time range of this highly
        stranded RNA (ssRNA). The polarity of this virus is positive-sense         pandemic, but the lesson that we have learnt from the history is
        ((+) ssRNA). Positive-sense viral RNA is similar to mRNA and               that the only way to fight the virus will not producenew vaccines,
        thus can be immediately translated by the host cell. Recombination         since the adaptation and the mutation of the virus is higher than
        in RNA viruses appears to be an adaptation for coping with genome          any knownones on earth. The only answer to end the pandemic, is
        damage. Recombination can occur infrequently between animal                the adaptation of human race to SARS-CoV-2 through Lamarckian
        viruses of the same species but of divergent lineages. The resulting       Evolution. This infectious disease with 7.8 billion people living
        recombinant viruses may sometimes cause an outbreak of infection           on earth is like playing with dices and the people contamination is
        in humans. RNA viruses have very high mutation rates. This is              random in mathematical Theorems. Some may adapt to the virus,
        one reason why it is difficult to make effective vaccines to prevent       some will die and the rest will be the carrier, therefore; the graph
        diseases caused by RNA viruses[215,216].                                   we predict is like The bean machine, a device invented by Francis
                                                                                   Galton shown below(Figure 11):
        Mathematical Calculation of SARS-CoV-2 and Future
        Concerns: The Factorial formula is:

                                                                                   Figure 11: The bean machine, a device invented by Francis Galton,
               The size of SARS-CoV-2 is approximately 0.3 microns[237].           can be called the first generator of normal random variables. This
        With conversion of Micrometer into nanometer, 0.3 will be 300              machine consists of a vertical board with interleaved rows of pins.
        nm in size. In page 21, we have described the Antigenic Drift of           Small balls are dropped from the top and then bounce randomly
        viruses especially SARS-CoV-2. The mathematical calculation of             left or right as they hit the pins. The balls are collected into bins at
        how many types of this virus exists is: 3 × 4, since we have 4 types       the bottom and settle down into a pattern resembling the Gaussian
        of mild coronavirus and 3 types of deadly with severe symptoms.            curve.
        So the numbers of different coronaviruses will be 3 × 4=12.
        Therefore; based on each type of virus is different from another                  According to the central limit theorem (more specifically,
        one, we use Factorial to measure all types of coronavirus which            the de Moivre-Laplace theorem), the binomial distribution
        exists on earth till now without the concern of the mutation in vivo       approximates the normal distribution provided that the number of
        of the virus. It is 12!=479001600. Overall, the number of different        rows and the number of balls are both large. Varying the rows will
        SARS-CoV-2 is about 479001600. Each of these kinds of viruses              result in different standard deviations or widths of the bell-shaped
                                                                                   curve or the normal distribution in the bins [219].

        Citation: Niknamian S and Zaminpira S (2020) The Historical/Evolutionary Cause and Possible Treatment of Pandemic Covid-19 (Sars-Cov-2, 2019-Corona-
        virus). Ann Med &Surg Case Rep: AMSCR-100050

Ann Med & Surg Case Rep, an open access journal
ISSN: 2652-4414
18                                                                                                                              Volume 02; Issue 03

        2019-Corovirus Relation to Fibonacci Sequence: The Fibonacci numbers, commonly denoted Fn, is a function called the Fibonacci
        sequence, means each number is the sum of the two preceding numbers, starting from 0 and 1:

              And the sequence is: We have collected the infected people with COVID-19. If we suppose each infected individual infects one
        other individual each day and at the end of day-two recovers fully or dies (we are interested in the number of people who are actively
        infected and alive). So the time stamps are the beginning of day-one, at the end of day-one and at the end of day-two. According to our
        model, an infected individual can infect one other person at the end of day-one and at the end of day-two. If we go on through time
        (days), the table below shows the result of infected people (Figure 12-14).

                                          Figure 12: The right vertical numbers shows the infected people per day.

                                       Figure 13: The number of infected people through time (day) by COVID-19.

        Citation: Niknamian S and Zaminpira S (2020) The Historical/Evolutionary Cause and Possible Treatment of Pandemic Covid-19 (Sars-Cov-2, 2019-Corona-
        virus). Ann Med &Surg Case Rep: AMSCR-100050

Ann Med & Surg Case Rep, an open access journal
ISSN: 2652-4414
19                                                                                                                             Volume 02; Issue 03

                                                                                   of the genome is a virus-encoded protein, and like mammalian
                                                                                   mRNA, there is a 3’ poly-A tail. Structural proteins are encoded in
                                                                                   the 5’ region of the genome and nonstructural at the 3’ end. This is
                                                                                   the same for all picornaviruses. The viral particles themselves are
                                                                                   not enveloped and are icosahedral in structure. The viral proteins
                                                                                   are translated as a single, long polypeptide, which is cleaved
                                                                                   into the structural and nonstructural viral proteins [212]. Human
                                                                                   rhinoviruses are composed of a capsid that contains four viral
                                                                                   proteins, VP1, VP2, VP3 and VP4.VP1, VP2, and VP3 form the
                                                                                   major part of the protein capsid. The much smaller VP4 protein
                                                                                   has a more extended structure, and lies at the interface between the
                                                                                   capsid and the RNA genome. There are 60 copies of each of these
                                                                                   proteins assembled as an icosahedron. Antibodies are a major
                                                                                   defense against infection with the epitopes lying on the exterior
                                                                                   regions of VP1-VP3. Human rhinovirus is most contagious during
                                                                                   the autumn and winter months. The virus can remain activated for
                                                                                   up to 3 hours outside of a human host. Once the virus is contracted,
                                                                                   a person is most contagious within the first 3 days. Preventive
         Figure 14: The Graph of Fibonacci and Pandemic of COVID-19.               measures such as regular vigorous hand washing with soap and
                                                                                   water may aid in avoiding infection. Avoiding touching the mouth,
             Therefore; the formula of infected people per day is:                 eyes and nose, the most common entry points for rhinovirus,
                              (for n > 2), which is the formula of                 may also aid in prevention. Droplet precautions, which take the
        Fibonacci series.                                                          form of a surgical mask and gloves, is the method used in major
                                                                                   hospitals.[243] [214,215].As mentioned, through our analysis, the
        Viruses Related to COVID-2019                                              most related virus to COVID-2019, is Rhinovirus which has very
                                                                                   similar in Structure, Genome, Size and symptoms of the SARS-
              There are some viruses that causes respiratory infection.            CoV-2. There has not been an effective anti-viral vaccination of
        Enteroviruses, Poliovirus, coxsackie, echovirus and Human                  this virus either.
        orthopneumovirus. Hence; none of them has been related to 2019-
        Coronavirus. Since their Signs and symptoms, Structure, Genome,                   There is a high possibility of mutation in this virus into 2019-
        Evolution, Taxonomy and Transmission are not similar to the                Coronavirus. In 2018, a new series of anti-rhinoviral compounds
        new COVID-2019. The only virus that has been correlated with               were reported by researchers at Imperial College London and
        COVID-2019 is Rhinovirus. The rhinovirus is the most common                colleagues at the University of York and the Pirbright Institute.
        viral infectious agent in humans and is the predominant cause              These molecules target human N-myristoyltransferase, an enzyme
        of the common cold and flu. Rhinovirus infection proliferates in           in the host cell which picornavirus requires in order to assemble
        temperatures of 33-35 °C (91-95 °F), the temperatures found in             its viral capsid, and thus generate an infectious virion. The lead
        the nose. The three species of rhinovirus (A, B, and C) include            compound in this series, IMP-1088, very potently inhibited host
        around 160 recognized types of human rhinovirus that differ                myristoylation of viral capsid protein and prevented infectious
        according to their surface proteins (serotypes) They are lytic in          virus formation, rescuing the viability of cells in culture which had
        nature and are among the smallest viruses, with diameters of about         been exposed to a variety of rhinovirus serotypes, or to related
        30 nanometers. By comparison, other viruses, such as smallpox              picornaviruses including poliovirus and foot-and-mouth-disease
        and vaccinia, are around ten times larger at about 300 nanometers          virus. Because these compounds target a host factor, they are
        (the same diameter as COVID-2019 which is 300 nanometers in                broadly active against all serotypes, and it is thought to be unlikely
        size)[220].                                                                that they can be overcome by resistance mutations in the virus.
              There are two modes of transmission: via aerosols of                 The main Cause of COVID-19 Pandemic
        respiratory droplets and from fomites (contaminated surfaces),
        including direct person-to-person contact. Rhinoviruses are                Through the lines and statements in this article, we hypothesize
        spread worldwide and are the primary cause of the common cold.             that the prime cause of SARS-CoV-2 is:
        Symptoms include sore throat, runny nose, nasal congestion,                •    The coevolution and Red Queen effect between mammals
        sneezing and cough. Those most affected by rhinoviruses are                     including humans and viruses. coevolution occurs when two
        infants, the elderly, and immune compromised people (Most elderly               or more species reciprocally affect each other’s evolution
        and Children). Human rhinoviruses preferentially grow at 32 °C                  through the process of natural selection and the Red Queen
        (89 °F), notably colder than the average human body temperature                 effect which is an evolutionary hypothesis that proposes
        of 37 °C (98 °F); hence the virus’s tendency to infect the upper                organisms must constantly adapt, evolve, and proliferate in
        respiratory tract, where respiratory airflow is in continual contact            order to survive while pitted against ever-evolving opposing
        with the (colder) extrasomatic environment [221].                               organisms in a constantly changing environment, as well as
             Rhinoviruses have single-stranded positive sense RNA                       to gain reproductive advantage. Increasing human population,
        genomes of between 7200 and 8500 nt in length. At the 5’ end                    antibiotic resistance, antiviral resistance, malnutrition, immune

        Citation: Niknamian S and Zaminpira S (2020) The Historical/Evolutionary Cause and Possible Treatment of Pandemic Covid-19 (Sars-Cov-2, 2019-Corona-
        virus). Ann Med &Surg Case Rep: AMSCR-100050

Ann Med & Surg Case Rep, an open access journal
ISSN: 2652-4414
20                                                                                                                              Volume 02; Issue 03

             deficiency (basically nutrition low in sulfur), low adaptation of     to viruses and the ability of Il-2 to induce those cells - even in ultra-
             human in their environment (Lamarckian Evolution) andhigh             low doses. Interestingly, a resident NK cell population is present
             adaptation of viruses with human genome [220].                        in the human lung and may provide early and important control
                                                                                   of viral infection (Cooper et al., 2018). Moreover, NK cells also
        •    The main cause of SARS-CoV-2 is through natural selection             exhibit activity against a variety of bacteria, e.g., by secretion of
             and Lamarckian Evolution Both which caused this RNA virus             the soluble molecules perforin and granulysin. Mice infected with
             so powerful and different in the nations worldwide. The first         Shigella and lacking B and T cells but with normal NK cells have
             Pandemic of Influenza was detected in 1732 and this virus             higher survival rates and lower bacterial titers than mice which
             evolved through natural selection till 2019 through Drift and         lack all three cell types. This suggests that phage-induced Il-2
             Assortment of SARS-CoV-1 and Influenza viruses which                  dependent activation of NK-mediated antimicrobial activity may
             caused the worldwide pandemic of SARS-CoV-2. [45,46].                 contribute to beneficial effects of PT, especially during prolonged
             There may be a correlation between Rhinoviruses and COVID-            phage administration cumulative median duration of successful
             19 which has not been studied yet and should be considered            phage therapy is 43 days. NK cells could be a promising agent in
             [221].                                                                antimicrobial immunotherapy, as data strongly suggest that these
        The Possible Treatment of COVID-19 (SARS-CoV-2)                            cells are active against not only viral but also bacterial and fungal
                                                                                   pathogens.
               Based on our research/Review of many major researches,
        there has not been any antiviral vaccines against these viruses            Acknowledgement
        and no antiviral drugs will be useful against COVID-19 since the
        adaptation and high mutation of this virus will not let these drugs               We would like to thank Senator Mark R Warner, Senator Tim
        be effective. The prime possible treatment Inhalation of ozone and         Kaine and Representative Ben Cline for their inspirational help
        sulfur dioxide, increasing L-Glutathione Plus Viral Phage Therapy          and dedication their time and help to the United States of America.
        (VFT) is the possible prime treatment of this disease. Finding the         Also, we would like to thank Mrs. Fallon Morell the President of
        right Phage Therapy is very hard in any viral infections since this        Weston A Price Foundation (WAPF), Professor Stephanie Seneff
        therapy was mainly used against bacterial infections. However;             (senior research scientist at the Computer Science and Artificial
        through our research and findings we have concluded that substantial       Intelligence Laboratory (CSAIL), ‎Massachusetts Institute of
        dose-dependent inhibition by T4 phage of adsorption of HAdV                Technology), Professor Thomas N Seyfried (Morrissey College of
        to both A549 and HEK293 cell lines in vitro LPS was without                Arts and Sciences) and Professor Dominic D’Agostino (Research
        effect. Moreover, T4 phage protected A549 cells from anHAdV-               Scientist, Inst. Human and Machine Cognition, Professor, College
        induced cytopathic effect. These data suggest that T4 phage could          of Medicine Molecular Pharmacology & Physiology, Morsani
        be considered as a potential novel antiviral agent. The capacity of        College of Medicine, Molecular Pharmacology & Physiology for
        the phage to inhibit HAdV infection at the stage of viral replication      their motivational help in my beginning of our first research till
        suggests that phage could also interfere with viruses using cellular       now.
        receptors other than those used by HAdV. Notably, the anti-viral
        effect of phage was measured as the decrease of the end-point
                                                                                   Conclusion
        HAdV infectious titer. Further in vitro studies were carried out on               In this Research/Review articles, we have gone through
        the effects of T4 and the staphylococcal phage A5/80 on HAdV               all the cases and epidemic of all the fatal diseases from the first
        DNA synthesis (real-time PCR) and the expression of its early and          time mentioned in history including Flu/Influenza pandemicuntil
        late genes (measured at the level of mRNA synthesis) in an A549            2020. Based on our research, the only period of time when there
        cell culture. Continuous incubation of adenovirus-infected cells           was no outbreak of influenza, RNA viruses or infectious diseases
        with T4 phage significantly reduced the level of adenoviral DNA            were during World War 2, where German scientists controlled
        synthesis (this effect was not observed with the staphylococcal            the epidemic of any virus infectionswhich should be noted by
        phage). Incubation with a high titer of T4 phage was required for          the scientists and researchers. The mutation of the SARS-CoV
        inhibition of HAdV early gene expression. Late adenoviral gene             and Influenza viruses is the main cause of SARS-CoV-2 through
        expression was reduced by preincubation (application of phage              natural selection and Lamarckian Evolution Both which caused
        prior to HAdV infection) and Coincubation with both phages when            this RNA virus so powerful and different in the nations worldwide.
        a low HAdV titer was used. In contrast, when a high HAdV titer             The first Pandemic of Influenza was first detected in 1732 and this
        was applied, both incubation and preincubation with T4 phage               virus evolved through natural selection till 2019 which caused the
        were inhibitory whilst a staphylococcal phage was inhibitory only          worldwide pandemic of SARS-CoV-2. Based on many studies,
        when continuous incubation with cells was applied. Those results           inhalation of Ozone plus Sulfur Dioxide, increasing the amounts
        suggest that the inhibitory effect of phage on HAdV infection may          of L-Glutathione (Which is low in children and older adults) plus
        differ and may be partially explained by their influence on the            Viral Phage Therapy (VPT)can be the prime treatment of SARS-
        expression of early and late adenoviral genes. When the effect of          CoV-2 infection. The seasonal temperature cannot be useful
        both phages on the expression of genes involved in antimicrobial           in controlling or reducing the pandemic of this virus since the
        immunity by the A549 cell line from human lung was studied, the            temperature rises gradually and the natural selection, Lamarckian
        most striking phenomenon was marked (>10-fold) enhancement                 Evolution and high mutation rate of the virus helps its survival. In
        of a gene coding for interleukin-2 (Il-2) by a staphylococcal phage        our mathematical calculation, the number of infected people is/will
        (Borysowski et al., 2018). This effect is of particular interest in the    be 1248000000 which should not be ignored by the scientists. We
        context of the well-known role of NK cells in the immune response          also introduced the Fibonacci Model in calculating the infected/

        Citation: Niknamian S and Zaminpira S (2020) The Historical/Evolutionary Cause and Possible Treatment of Pandemic Covid-19 (Sars-Cov-2, 2019-Corona-
        virus). Ann Med &Surg Case Rep: AMSCR-100050

Ann Med & Surg Case Rep, an open access journal
ISSN: 2652-4414
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